Does the Reduction of Total Body Iron Storage (TBIS) Alter Mortality in a Population of Patients With Advanced PVD? (FeAST)

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ClinicalTrials.gov Identifier: NCT00032357

Recruitment Status :
Completed

First Posted : March 20, 2002

Last Update Posted : January 21, 2013

Sponsor:

US Department of Veterans Affairs

Information provided by (Responsible Party):

VA Office of Research and Development ( US Department of Veterans Affairs )

Mortality [ Time Frame: The minimum follow-up was 3.5 years and maximum follow-up was 6 years ]

The primary objective of this study is to evaluate the effectiveness of a reduction of Total Body Iron Stores (TBIS) in decreasing the rate of all cause mortality in patients with peripheral vascular disease (PVD).

Does the Reduction of Total Body Iron Storage (TBIS) Alter Mortality in a Population of Patients With Advanced PVD?

Official Title ICMJE

CSP #410 - The Iron (Fe) and Atherosclerosis Study (FeAST)

Brief Summary

Veterans Affairs Cooperative Study #410, The Iron and Atherosclerosis Trial, FeAST, a 24-hospital prospective randomized single-blinded clinical trial of graded iron reduction was conducted between May 1, 1999 and April 30, 2005, and has now been completed. A total of 1,277 primarily male participants with peripheral arterial disease were entered. The primary outcome was all cause mortality and the secondary outcome combined death plus non-fatal myocardial infarction (MI) and stroke.

Detailed Description

The original JAMA abstract (2007) reported no overall effect of iron reduction intervention by phlebotomy. However, pre-planned analyses according to randomization variables at entry, including age and ferritin level, were described in the JAMA paper showing improved outcomes with iron reduction with younger age by quartile for the secondary endpoint (p for interaction =0.004) and also suggested a favorable effect in smokers (p for interaction 0.006). Age analyzed as a continuous variable using the Cox proportional hazards regression model and log relative hazard plots revealed that age interacted nonlinearly with treatment in both primary (p=0.04) and secondary (p<0.001) outcomes. The Cox model showed improved primary (HR 0.47, 95% CI 0.24-0.90, p=0.02) and secondary (HR 0.41, 95% CI 0.24-0.68, p<0.001) outcomes in youngest age quartile participants (age 43 to 61) randomized to iron reduction versus control. Thus, an interaction between age and level of body iron may have masked beneficial effects of iron reduction in the overall cohort.

A possible effect of iron levels on risk of cancer as well as vascular disease was recognized at trial inception. Participants with visceral malignancy within the preceding five years were excluded from this study. However, information was collected prospectively on the occurrence of new visceral malignancy and cause-specific mortality including death due to cancer. As reported in the Journal of the National Cancer Institute, a new visceral malignancy was diagnosed during follow-up in 60 control and 38 iron reduction participants, a 37% (HR 0.63; 95% CI = 0.42 - 0.95, p = 0.026) decrease in risk with iron reduction. Reduced cancer risk with iron reduction was confirmed on time-to-event analysis (HR = 0.65; 95% CI = 0.43 - 0.97, p = 0.036). Reduced risk was observed for several common tumor types. Iron reduction participants had lower cancer - specific mortality and lower all-cause mortality in participants diagnosed with cancer (HR = 0.39; 95% CI = 0.21 - 0.72, p = 0.003 and HR = 0.49; 95% CI = 0.29 - 0.83, p = 0.009 respectively), compared to control participants. MFFL during follow-up in those participants randomized to iron reduction who developed cancer were comparable to levels in control participants (t93 = 0.8, p = 0.428). The MFFL in participants randomized to iron reduction developing cancer was 127 ng/mL, 95% CI = 71.2 - 183.0. The MFFL was significantly lower in participants not developing cancer, 76.4 ng/mL, 95% CI = 71.4 - 81.4, p = 0.017). Participants randomized to iron reduction developing cancer appeared to be relatively non-compliant with intervention.

Analysis of data from the FeAST study continues to delineate interactions between iron status and smoking, lipid levels and statin use, diabetes and race. It has been shown that ferritin levels ranging from about 70 to 79 ng/mL are associated with lower mortality and levels of inflammatory markers. Statin use, while not a randomization variable, has been monitored and shown to relate to lower ferritin levels.

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Completed

Actual Enrollment ICMJE (submitted: November 21, 2012)

1277

Original Enrollment ICMJE (submitted: June 23, 2005)

1600

Actual Study Completion Date

September 2005

Actual Primary Completion Date

April 2005 (Final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Males over the age of 21 years and post menopausal (either natural or surgical) females with a diagnosis of intermittent claudication who are not scheduled for major surgery and who can give informed consent will be entered.

Hematocrit of 30% or greater for females and 35% or greater for males, normal liver function, serum creatinine less than 4 mg/dl. Patients with mild anemia and mild creatinine elevation will be entered (provided the anemia is not due to Fe deficiency found on screening laboratory tests) because such findings are commonly present chronically in PVD.

Patients will not be excluded on the basis of either the existence or severity of either coronary- or cerebrovascular disease, medication use including non-steroidal anti-inflammatory drugs and anticoagulants, coronary angiographic findings, previous history of or possible future need for angioplasty or coronary bypass surgery, or elevated blood pressure.

Patients must agree to not take any Fe supplements or vitamins while on study.

Exclusion Criteria:

1. Patients must have at least one lower extremity and must not be on another experimental therapy protocol for atherosclerotic vascular disease.

Sex/Gender

Sexes Eligible for Study:

All

Ages

21 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Contacts ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ICMJE

Puerto Rico, United States

Removed Location Countries

Administrative Information

NCT Number ICMJE

NCT00032357

Other Study ID Numbers ICMJE

410

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement

Not Provided

Responsible Party

VA Office of Research and Development ( US Department of Veterans Affairs )